Intraocular pressure reducing prostaglandin-like 7-oxabicyclo derivatives

Abstract

Disclosed are a method and composition for treating ocular hypertension. The compositions comprise prostaglandin-like 7-oxabicyclo derivatives which have been discovered to exhibit a pronounced intraocular pressure reducing effect, but with substantially reduced adverse side effects characteristic of the corresponding prostaglandin.

I claim: 
     
       1. A method of treating ocular hypertension which comprises administering to a mammal having ocular hypertension a therapeutically effective amount of a compound of formula (I) ##STR11## or an isomer thereof, wherein Z 1  is an --RCOOR 1  group in the β configuration, wherein R is an alkyl or alkenyl group having up to 10 carbon atoms, R 1  is selected from the group consisting of hydrogen, an aliphatic radical of from one to 10 carbon atoms and a cation which forms a pharmaceutically acceptable salt; Z 2  is --CH═CH--CH(OR 2 )R 3  in the ∝ configuration, wherein R 2  is hydrogen or an acyl group having from one to 6 carbon atoms, and R 3  is selected from the group consisting of cycloalkyl having 5 or 6 carbon atoms, aryl and aralkyl each having 5 or 6 carbon atoms in the aryl moiety. 
     
     
       2. The method of claim 1 wherein R 3  is cyclohexane. 
     
     
       3. The method of claim 1 wherein R 2  is hydrogen. 
     
     
       4. The method of claim 2 wherein R is an alkyl or alkenyl group having 4 to 8 carbon atoms. 
     
     
       5. The method of claim 4 wherein R is an alkyl or alkenyl group having 6 carbon atoms. 
     
     
       6. The method of claim 1 wherein Z 1  is 7-carboxyl-hept-2-yl. 
     
     
       7. The method of claim 1 wherein Z 2  is 3-cyclohexyl-3-hydroxy-1-propenyl. 
     
     
       8. The method of claim 1 wherein Z 2  is 3-hydroxy-4-phenyl-1-butenyl. 
     
     
       9. The method of claim 1 wherein Z 2  is 3-hydroxy-4-(3-thienyl)-1-butenyl. 
     
     
       10. The method of claim 1 wherein said compound of formula (I) is selected from the group consisting of [1β,2β(5Z),3∝(1E,3S*),4β]-7-[3-Cyclohexyl-3-hydroxy-1-propenyl)-7-oxabicyclo[2.2.2]hept-2-yl]-5-heptenoic acid;   [1β,2β(5Z),3∝(1E,3S*),4β]-7-[3-(3-hydroxy-4-phenyl-1-butenyl)-7-oxabicyclo[2.2.1]hept-2-yl]-5-heptenoic acid;   
     
     
       [β . 2β(5Z),3∝(1E,3S*),4β]-7-[3-[3-hydroxy-4-(3-thienyl)-1-butenyl]-7-oxabicyclo[2.2.1]hept-2-yl]-5-heptenoic acid, and pharmaceutically acceptable esters and salts of these compounds.